Product information to be updated for phenobarbital medicines used to treat epilepsy in animals
The European expert group on veterinary medicines, the CMDv, considers that the active substance phenobarbital is associated with several newly identified adverse reactions in dogs and cats.
The Danish Medicines Agency led the assessment process within the Coordination Group for Mutual Recognition and Decentralised Procedures for Veterinary Medicinal Products (CMDv).
The expert group reviewed adverse event reports and relevant literature relating to veterinary medicinal products containing the active substance phenobarbital — that is, medicines used to treat epilepsy.
Main conclusions of the CMDv
Following its review, the CMDv considers that the benefits of treatment with phenobarbital-containing veterinary medicinal products continue to outweigh the risks of adverse events. However, CMDv recommends updating the product information to include the possible adverse reactions of pancreatitis and elevated liver enzymes in dogs.
The CMDv also recommends monitoring serum lipids in dogs receiving phenobarbital.
In addition, the CMDv found that there is an association between treatment with phenobarbital and the serious reaction known as ‘anticonvulsant hypersensitivity syndrome’ (AHS) in cats. A similar association could not be established with sufficient certainty in dogs, so the reaction will remain under close monitoring in dogs.
Recommended updates to the product information
Pancreatitis is to be included as an ‘uncommon’ adverse event, in cases where phenobarbital is used alone. All product informations will also specify that concomitant treatment with phenobarbital and potassium bromide further increases the risk of pancreatitis.
Elevated liver enzymes are recommended for inclusion as a ‘common’ adverse event, with a clarification that this finding does not necessarily indicate impairment of liver function.
Recommendations for regular monitoring of serum lipids are to be added as a special precaution, as elevated serum lipid levels are associated with an increased risk of other diseases, including pancreatitis.
Important information for veterinarians throughout the EU about ‘anticonvulsant hypersensitivity syndrome’
The review indicates an association between treatment with phenobarbital and the development of ‘anticonvulsant hypersensitivity syndrome’ (AHS), also known as ‘pseudolymphoma’, in cats.
This is a serious, but often reversible, adverse event that is likely to be extremely rare. Reversible means that the adverse reaction improves or the animal recovers completely when treatment is stopped.
None of the phenobarbital-containing veterinary medicinal products currently marketed in the EU are authorised for the treatment of cats. Phenobarbital use in cats is therefore currently outside the terms of the marketing authorisation, and use therefore falls under for example Article 112 of the Veterinary Medicines Regulation (the ‘cascade rule’).
The CMDv therefore recommends that veterinarians throughout the EU are informed of the risk of AHS associated with using phenobarbital-containing medicines in cats through other means than updating the product information.
The Pharmacovigilance Working Party (PhVWP-V) will prepare further information for veterinarians in due course.
At the same time, the expert surveillance group under the PhVWP-V will continue to closely monitor cases of possible AHS in dogs.